合成路线1

In a nonoxidative coupling sytrategy, the required tetracyclic precursor (X) has been prepared by two methods. Alkylation of thiolactam (I) with 2 (bromomethyl)-1-butene (II) gives the thioiminium salt (III), which undergoes thio-Claisen rearrangement in the presence of DBU in THF to produce (IV) as a mixture of cis and trans isomers. After conversion of thiolactams (IV) into the corresponding lactams with m-chloroperoxybenzoic acid (mCPBA), the desired isomer (V) is isolated employing preparative HPLC. Double bond dihydroxylation with N-methylmorpholine-N-oxide in the presence of a catalytic amount of OsO4 leads to diol (VI) as a diastereomeric mixture. Protection of diols (VI) with 1-methoxycyclohexene (VII) affords the corresponding mixture of cyclohexylidene ketals (VIII). After conversion of (VIII) to the respective thiolactams with Lawesson's reagent in hot toluene, separation of isomers employing preparative HPLC furnishes thiolactam (IX). Then, desulfuration of thiolactam (IX) by means of Raney nickel gives rise to intermediate (X) (7).